Herpesvirus saimiri (H. saimiri) is a lymphotropic or gamma herpesvirus and causes malignant lymphomas of monkeys. Epstein-Barr virus (EBV) is also a lymphotropic herpesvirus and is a well recognized cause of malignant lymphomas of humans; EBV is related to H. saimiri in the arrangement of its genes. The principal hypothesis of this research plan is that gene products of H. saimiri activate lymphokines and activation of lymphokines contribute to oncogenic transformation. The experimental approach of the planned studies is based on three novel findings; (i) A strain of H. saimiri is highly oncogenic in rabbits; evaluation of H. saimiri mutants now can be done without the use of primate species. (ii) Rabbit lymphocytes transformed by the highly oncogenic strain contain a 1.2 KB polyadenylated RNA and four small U-like RNAs transcribed from a 4 KB region of the genome involved in oncogenic transformation. (iii) H. saimiri transformed lymphocytes secrete IL-4 and express large numbers of IL-2 receptors. AIM 1. Characterize the 1.2 KB RNA and small Unlike RNAS. The RNAs will be mapped, and the nucleotide sequence will be determined. AIM 2. Identify the putative protein encode by the 1.2 KB RN.A Sequences-of the 1.2 KB RNA will be expressed in E. coli and fusion proteins will be used to immunize rabbits. Subcellular localization of the putative protein in transformed lymphocytes will be tested by immunofluorescence, the size of the protein will be determined. AIM 3. Identify the gene(s) contribute to the oncogenicity of a highly oncogenic strain. Recombinant viruses will be constructed; cloned DNA fragments of a highly oncogenic strain will be introduced into the genome of another strain which is nononcogenic in New Zealand white rabbits. oncogenic potential of recombinant viruses will be tested in rabbits. AIM 4. Test recombinant viruses for activation of lymphokines, We will test whether secretion of IL-4 and expression of IL-2 receptors is stimulated by infection/superinfection with a panel of recombinant viruses. AIM 5. Test which viral gene(s) can activate lymphokines. The first approach will be to express cloned viral genes in lymphocytes and test whether these viral genes stimulate secretion of IL-4 and expression of IL-2 receptor. The second approach will test whether cloned viral genes can trans-activate cis-acting regulatory elements of lymphokine genes.